A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, whereas extra-hypothalamic CRH has a ...key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma adrenocorticotropic hormone, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open-field, elevated plus maze, holeboard, light-dark box and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation.
Recent developments in Geant4 Allison, J.; Amako, K.; Apostolakis, J. ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
11/2016, Letnik:
835, Številka:
C
Journal Article
Recenzirano
Odprti dostop
Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including ...high energy physics, astrophysics and space science, medical physics and radiation protection. Over the past several years, major changes have been made to the toolkit in order to accommodate the needs of these user communities, and to efficiently exploit the growth of computing power made available by advances in technology. The adaptation of Geant4 to multithreading, advances in physics, detector modeling and visualization, extensions to the toolkit, including biasing and reverse Monte Carlo, and tools for physics and release validation are discussed here.
•Multithreading resulted in a smaller memory footprint and nearly linear speed-up.•Scoring options, faster geometry primitives, more versatile visualization were added.•Improved electromagnetic and hadronic models and cross sections were developed.•Reverse Monte Carlo and general biasing methods were added.•Physics validation efforts were expanded and new validation tools were added.
The chemical properties of an element are primarily governed by the configuration of electrons in the valence shell. Relativistic effects influence the electronic structure of heavy elements in the ...sixth row of the periodic table, and these effects increase dramatically in the seventh row--including the actinides--even affecting ground-state configurations. Atomic s and p1/2 orbitals are stabilized by relativistic effects, whereas p3/2, d and f orbitals are destabilized, so that ground-state configurations of heavy elements may differ from those of lighter elements in the same group. The first ionization potential (IP1) is a measure of the energy required to remove one valence electron from a neutral atom, and is an atomic property that reflects the outermost electronic configuration. Precise and accurate experimental determination of IP1 gives information on the binding energy of valence electrons, and also, therefore, on the degree of relativistic stabilization. However, such measurements are hampered by the difficulty in obtaining the heaviest elements on scales of more than one atom at a time. Here we report that the experimentally obtained IP1 of the heaviest actinide, lawrencium (Lr, atomic number 103), is 4.96(+0.08)(-0.07) electronvolts. The IP1 of Lr was measured with (256)Lr (half-life 27 seconds) using an efficient surface ion-source and a radioisotope detection system coupled to a mass separator. The measured IP1 is in excellent agreement with the value of 4.963(15) electronvolts predicted here by state-of-the-art relativistic calculations. The present work provides a reliable benchmark for theoretical calculations and also opens the way for IP1 measurements of superheavy elements (that is, transactinides) on an atom-at-a-time scale.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
The superheavy element with atomic number Z=117 was produced as an evaporation residue in the (48)Ca+(249)Bk fusion reaction at the gas-filled recoil separator TASCA at GSI Darmstadt, Germany. The ...radioactive decay of evaporation residues and their α-decay products was studied using a detection setup that allowed measuring decays of single atomic nuclei with half-lives between sub-μs and a few days. Two decay chains comprising seven α decays and a spontaneous fission each were identified and are assigned to the isotope (294)117 and its decay products. A hitherto unknown α-decay branch in (270)Db (Z = 105) was observed, which populated the new isotope (266)Lr (Z = 103). The identification of the long-lived (T(1/2) = 1.0(-0.4)(+1.9) h) α-emitter (270)Db marks an important step towards the observation of even more long-lived nuclei of superheavy elements located on an "island of stability."
Experimental investigations of transactinoide elements provide benchmark results for chemical theory and probe the predictive power of trends in the periodic table. So far, in gas-phase chemical ...reactions, simple inorganic compounds with the transactinoide in its highest oxidation state have been synthesized. Single-atom production rates, short half-lives, and harsh experimental conditions limited the number of experimentally accessible compounds. We applied a gas-phase carbonylation technique previously tested on short-lived molybdenum (Mo) and tungsten (W) isotopes to the preparation of a carbonyl complex of seaborgium, the 106th element. The volatile seaborgium complex showed the same volatility and reactivity with a silicon dioxide surface as those of the hexacarbonyl complexes of the lighter homologs Mo and W. Comparison of the product’s adsorption enthalpy with theoretical predictions and data for the lighter congeners supported a Sg(CO)₆ formulation.
A model for the simulation of orientational effects in straight and bent periodic atomic structures is presented. The continuum potential approximation has been adopted. The model allows the ...manipulation of particle trajectories by means of straight and bent crystals and the scaling of the cross sections of hadronic and electromagnetic processes for channeled particles. Based on such a model, an extension of the Geant4 toolkit has been developed. The code has been validated against data from channeling experiments carried out at CERN.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Geant4 developments and applications Allison, J.; Amako, K.; Apostolakis, J. ...
IEEE transactions on nuclear science,
02/2006, Letnik:
53, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Geant4 is a software toolkit for the simulation of the passage of particles through matter. It is used by a large number of experiments and projects in a variety of application domains, including ...high energy physics, astrophysics and space science, medical physics and radiation protection. Its functionality and modeling capabilities continue to be extended, while its performance is enhanced. An overview of recent developments in diverse areas of the toolkit is presented. These include performance optimization for complex setups; improvements for the propagation in fields; new options for event biasing; and additions and improvements in geometry, physics processes and interactive capabilities
To evaluate disparities in cardiovascular risk factors among Asians and Native Hawaiians and other Pacific Islanders (NHPI) in Hawaii who are hospitalized with ischemic stroke.
We performed a ...retrospective study on consecutive patients hospitalized for ischemic stroke at a single tertiary center in Honolulu between 2004 and 2010. The prevalence of cardiovascular risk factors was compared for NHPI, Asians, and whites who were hospitalized for ischemic stroke.
A total of 1,921 patients hospitalized for ischemic stroke were studied. NHPI were less likely to be older (odds ratio OR 0.95, 95% confidence interval CI 0.94-0.96), more likely to be female (OR 1.55, 95% CI 1.07-2.24), and more likely to have diabetes (OR 2.74, 95% CI 1.87-4.00), hypertension (OR 1.98, 95% CI 1.27-3.10), and obesity (OR 1.82, 95% CI 1.25-2.65) than whites. NHPI had higher low-density lipoprotein levels (114 ± 50 mg/dL vs 103 ± 45 mg/dL, p = 0.001) and lower high-density lipoprotein levels (38 ± 11 mg/dL vs 45 ± 15 mg/dL, p < 0.0001) than whites. Compared with Asians, NHPI were less likely to be older (OR 0.95, 95% CI 0.94-0.97) and more likely to have diabetes (OR 1.88, 95% CI 1.35-2.61), previous stroke or TIA (OR 1.57, 95% CI 1.09-2.25), and obesity (OR 6.05, 95% CI 4.31-8.48).
Asians, NHPI, and whites with ischemic stroke have substantially different cardiovascular risk factors. Targeted secondary prevention will be important in reducing disparities among these racial groups.
Summary
Background
Keloid lesions are characterized by mesenchymal cell proliferation and excessive extracellular matrix deposition. Previous microarray analyses have been performed to investigate ...the mechanism of keloid development. However, the molecular pathology that contributes to keloid development remains obscure.
Aim
To explore the underlying essential molecules of keloids using microarrays.
Methods
We performed microarray analyses of keloid and nonlesional skin tissues both in vivo and in vitro. Gene expression levels were compared between tissues and cells. Quantitative reverse transcription (qRT)‐PCR and immunohistochemical staining were used to determine the expression levels of molecules of interest in keloid tissues.
Results
Several common molecules were upregulated in both keloid tissues and keloid‐lesional fibroblasts. PTPRD and NTM were upregulated both in vivo and in vitro. The genes MDFI and ITGA4 were located at the centre of the gene coexpression network analysis using keloid tissues. qRT‐PCR revealed significant expression levels of PTPRD and MDFI in keloid tissues. Immunopathological staining revealed that MDFI‐positive cells, which have fibroblast characteristics, were located in the keloid‐associated lymphoid tissue (KALT) portion of the keloid tissue.
Conclusion
Our gene expression profiles of keloids could distinguish the difference between lesional tissue and cultured lesional fibroblasts, and MDFI was found to be commonly expressed in both tissues and cells. Thus, MDFI‐positive cells, which were located in the KALT, may play an important role in keloid pathogenesis and thus might be useful for in vitro keloid studies.
Single crystal elastic constants of Ti–Ni alloys without (quenched) and with (aged) Ti
3Ni
4 precipitates were measured systematically by rectangular parallelepiped resonance method as a function of ...composition and temperature, and compared with Ti–Ni–Cu and Ti–Ni–Fe alloys, in an attempt to answer some long-standing questions as to the origin of the unique monoclinic B19′ martensite, and why composition and thermomechanical treatment greatly changes the path of martensitic transformation. The results showed that softening in
c
44, in additional to
c′, is a common feature for all Ti–Ni binary (both quenched or aged) and ternary alloys. This general feature just corresponds to the fact that all these alloys ultimately transform into B19′, suggesting that softening in
c
44 is responsible for the unique B19′ martensite, which found no analogy in other β phase alloys. We also found an interesting correspondence between the temperature dependence of anisotropy factor and transformation path. Prior to B2–B19′ transformation anisotropy shows a decrease with lowering temperature; prior to B2–B19 an anisotropy increase, while prior to B2–R transformation a constant anisotropy. We further showed that three possible martensite candidates (R, B19, B19′) are rooted in anomalies in specific phonon modes and elastic softening. We showed that the multi-stage transformations are restricted by a general rule: multi-stage transformation occurs in the sequence of increasing transformation strain. With this rule we can explain all known transformation paths by considering the effect of alloying addition and fine precipitates/dislocation network on relative stability of different martensites. We further predict that there may exist a new transformation path in Ti–Ni-based alloys: B2–R–B19–B19′.
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